Variant 1-151574969-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020127.3(TUFT1):c.782G>A(p.Arg261Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,422,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TUFT1
NM_020127.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

Variant links:

Genes affected

TUFT1 (HGNC:12422): (tuftelin 1) Tuftelin is an acidic protein that is thought to play a role in dental enamel mineralization and is implicated in caries susceptibility. It is also thought to be involved with adaptation to hypoxia, mesenchymal stem cell function, and neurotrophin nerve growth factor mediated neuronal differentiation. [provided by RefSeq, Aug 2014]

TUFT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108419925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUFT1	NM_020127.3 linkuse as main transcript	c.782G>A	p.Arg261Gln	missense_variant	9/13	ENST00000368849.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUFT1	ENST00000368849.8 linkuse as main transcript	c.782G>A	p.Arg261Gln	missense_variant	9/13	1	NM_020127.3	A1	Q9NNX1-1
TUFT1	ENST00000368848.6 linkuse as main transcript	c.707G>A	p.Arg236Gln	missense_variant	8/12	1		P4	Q9NNX1-2
TUFT1	ENST00000392712.7 linkuse as main transcript	c.617G>A	p.Arg206Gln	missense_variant	7/11	5
TUFT1	ENST00000490156.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

187522

Hom.:

AF XY:

0.0000100

AC XY:

AN XY:

99538

show subpopulations

Gnomad AFR exome

AF:

0.0000880

Gnomad AMR exome

AF:

0.0000722

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1422712

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000516

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000838

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.782G>A (p.R261Q) alteration is located in exon 9 (coding exon 9) of the TUFT1 gene. This alteration results from a G to A substitution at nucleotide position 782, causing the arginine (R) at amino acid position 261 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.093

T;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

0.55

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.028

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.18

B;.;B

Vest4

0.21

MVP

0.50

MPC

0.23

ClinPred

0.21

GERP RS

-0.70

Varity_R

0.053

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over